Post-COVID exercise intolerance is associated with capillary alterations and immune dysregulations in skeletal muscles

The SARS-CoV-2 pandemic not only resulted in millions of acute infections worldwide, but also in many cases of post-infectious syndromes, colloquially referred to as long COVID. Due to the heterogeneous nature of symptoms and scarcity of available tissue samples, little is known about the underlying mechanisms. We present an in-depth analysis of skeletal muscle biopsies obtained from eleven patients suffering from enduring fatigue and post-exertional malaise after an infection with SARS-CoV-2. Compared to two independent historical control cohorts, patients with post-COVID exertion intolerance had fewer capillaries, thicker capillary basement membranes and increased numbers of CD169+ macrophages. SARS-CoV-2 RNA could not be detected in the muscle tissues. In addition, complement system related proteins were more abundant in the serum of patients with PCS, matching observations on the transcriptomic level in the muscle tissue. We hypothesize that the initial viral infection may have caused immune-mediated structural changes of the microvasculature, potentially explaining the exercise-dependent fatigue and muscle pain.

Automated summary

This study conducted an in-depth analysis of skeletal muscle biopsies from eleven patients who experienced enduring fatigue and post-exertional malaise after being infected with SARS-CoV-2. The results showed that these patients had fewer capillaries, thicker capillary basement membranes, and increased numbers of CD169+ macrophages in their muscle tissues. SARS-CoV-2 RNA was not detected in the muscle tissues. Additionally, complement system related proteins were found to be more abundant in the serum of patients with post-COVID exertion intolerance, which matched observations on the transcriptomic level in the muscle tissue. The researchers hypothesize that the initial viral infection may have caused immune-mediated structural changes in the microvasculature, potentially explaining the exercise-dependent fatigue and muscle pain.